Liver fibrosis and cirrhosis, are conditions characterized by abnormal deposition of collagen within the hepatic lobule. These two conditions are the cause of significant morbidity and mortality in the United States. In spite of the dramatic advances in collagen biochemistry in the last decade, very little is known about the collagen types deposited in the liver, the cell(s) responsible for the synthesis of these collagens, or the role of fibronectin in fibrogenesis. We propose to study these problems in experimental liver fibrosis and cirrhosis, as well as in tissue culture of hepatocytes. The last part of the study will be performed on human biopsies. The basic approach will be electron immunohistochemistry, using monospecific antibodies against the different collagen types, I and III as well as basement membrane and AB collagens. The proposed studies will delineate: the collagen types present at different stages of the disease process; sequence of deposition and removal of the different collagen types; what hepatic cells are responsible for the synthesis and secretion of the different collagen types and fibronectin; the role of fibronectin in the fibrotic process and any possible interactions between the different stromal components and hepatic cells.